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Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3

The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and...

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Autores principales: Siddhuraj, Premkumar, Clausson, Carl-Magnus, Sanden, Caroline, Alyamani, Manar, Kadivar, Mohammad, Marsal, Jan, Wallengren, Joanna, Bjermer, Leif, Erjefält, Jonas S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913381/
https://www.ncbi.nlm.nih.gov/pubmed/33546258
http://dx.doi.org/10.3390/cells10020309
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author Siddhuraj, Premkumar
Clausson, Carl-Magnus
Sanden, Caroline
Alyamani, Manar
Kadivar, Mohammad
Marsal, Jan
Wallengren, Joanna
Bjermer, Leif
Erjefält, Jonas S.
author_facet Siddhuraj, Premkumar
Clausson, Carl-Magnus
Sanden, Caroline
Alyamani, Manar
Kadivar, Mohammad
Marsal, Jan
Wallengren, Joanna
Bjermer, Leif
Erjefält, Jonas S.
author_sort Siddhuraj, Premkumar
collection PubMed
description The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and protein expression at a single-cell level, the present study maps CPA3 mRNA and protein throughout the MCT and MCTC populations in healthy skin, gut and lung tissues. MCTC cells had both a higher frequency of CPA3 protein-containing cells and a higher protein-staining intensity than the MCT population. Among the tissues, skin MCs had highest CPA3 protein intensity. The expression pattern at the mRNA level was reversed. Lung mast cells had the highest mean CPA3 mRNA staining. Intriguingly, the large alveolar MCT population, that lack CPA3 protein, had uniquely high CPA3 mRNA intensity. A broader multi-tissue RNA analysis confirmed the uniquely high CPA3 mRNA quantities in the lung and corroborated the dissociation between chymase and CPA3 at the mRNA level. Taken together, our novel data suggest a hitherto underestimated contribution of mucosal-like MCT to baseline CPA3 mRNA production. The functional consequence of this high constitutive expression now reveals an important area for further research.
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spelling pubmed-79133812021-02-28 Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3 Siddhuraj, Premkumar Clausson, Carl-Magnus Sanden, Caroline Alyamani, Manar Kadivar, Mohammad Marsal, Jan Wallengren, Joanna Bjermer, Leif Erjefält, Jonas S. Cells Article The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and protein expression at a single-cell level, the present study maps CPA3 mRNA and protein throughout the MCT and MCTC populations in healthy skin, gut and lung tissues. MCTC cells had both a higher frequency of CPA3 protein-containing cells and a higher protein-staining intensity than the MCT population. Among the tissues, skin MCs had highest CPA3 protein intensity. The expression pattern at the mRNA level was reversed. Lung mast cells had the highest mean CPA3 mRNA staining. Intriguingly, the large alveolar MCT population, that lack CPA3 protein, had uniquely high CPA3 mRNA intensity. A broader multi-tissue RNA analysis confirmed the uniquely high CPA3 mRNA quantities in the lung and corroborated the dissociation between chymase and CPA3 at the mRNA level. Taken together, our novel data suggest a hitherto underestimated contribution of mucosal-like MCT to baseline CPA3 mRNA production. The functional consequence of this high constitutive expression now reveals an important area for further research. MDPI 2021-02-03 /pmc/articles/PMC7913381/ /pubmed/33546258 http://dx.doi.org/10.3390/cells10020309 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Siddhuraj, Premkumar
Clausson, Carl-Magnus
Sanden, Caroline
Alyamani, Manar
Kadivar, Mohammad
Marsal, Jan
Wallengren, Joanna
Bjermer, Leif
Erjefält, Jonas S.
Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3
title Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3
title_full Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3
title_fullStr Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3
title_full_unstemmed Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3
title_short Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3
title_sort lung mast cells have a high constitutive expression of carboxypeptidase a3 mrna that is independent from granule-stored cpa3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913381/
https://www.ncbi.nlm.nih.gov/pubmed/33546258
http://dx.doi.org/10.3390/cells10020309
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